The S. Typhi effector StoD is an E3 ubiquitin ligase which binds K48- and K63-linked di-ubiquitin

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Title: The S. Typhi effector StoD is an E3 ubiquitin ligase which binds K48- and K63-linked di-ubiquitin
Authors: Mylona, E
Frankel, G
Item Type: Journal Article
Abstract: Salmonella enterica (e.g., serovars Typhi and Typhimurium) relies on translocation of effectors via type III secretion systems (T3SS). Specialization of typhoidal serovars is thought to be mediated via pseudogenesis. Here, we show that the Salmonella Typhi STY1076/t1865 protein, named StoD, a homologue of the enteropathogenic Escherichia coli/enterohemorrhagic E. coli/Citrobacter rodentium NleG, is a T3SS effector. The StoD C terminus (StoD-C) is a U-box E3 ubiquitin ligase, capable of autoubiquitination in the presence of multiple E2s. The crystal structure of the StoD N terminus (StoD-N) at 2.5 Å resolution revealed a ubiquitin-like fold. In HeLa cells expressing StoD, ubiquitin is redistributed into puncta that colocalize with StoD. Binding assays showed that StoD-N and StoD-C bind the same exposed surface of the β-sheet of ubiquitin, suggesting that StoD could simultaneously interact with two ubiquitin molecules. Consistently, StoD interacted with both K63- (KD = 5.6 ± 1 μM) and K48-linked diubiquitin (KD = 15 ± 4 μM). Accordingly, we report the first S. Typhi–specific T3SS effector. We suggest that StoD recognizes and ubiquitinates pre-ubiquitinated targets, thus subverting intracellular signaling by functioning as an E4 enzyme.
Issue Date: 1-Jun-2019
Date of Acceptance: 10-May-2019
ISSN: 2575-1077
Publisher: Life Science Alliance
Journal / Book Title: Life Science Alliance
Volume: 2
Issue: 3
Copyright Statement: © 2019 McDowell et al. article is available under a Creative Commons License (Attribution 4.0 International, as described at
Sponsor/Funder: Wellcome Trust
Biotechnology and Biological Sciences Research Council (BBSRC)
Funder's Grant Number: 107057/Z/15/Z
Publication Status: Published
Article Number: e201800272
Online Publication Date: 2019-05-29
Appears in Collections:Faculty of Natural Sciences

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